title: Mitochondrial function and increased convective O2 transport: implications for the assessment of mitochondrial respiration in vivo.
abstract: Although phosphorus magnetic resonance spectroscopy (31P-MRS)-based evidence suggests that in vivo peak mitochondrial respiration rate in young untrained adults is limited by the intrinsic mitochondrial capacity of ATP synthesis, it remains unknown whether a large, locally targeted increase in convective O2 delivery would alter this interpretation. Consequently, we examined the effect of superimposing reactive hyperemia (RH), induced by a period of brief ischemia during the last minute of exercise, on oxygen delivery and mitochondrial function in the calf muscle of nine young adults compared with free-flow conditions (FF). To this aim, we used an integrative experimental approach combining 31P-MRS, Doppler ultrasound imaging, and near-infrared spectroscopy. Limb blood flow [area under the curve (AUC), 1.4 ± 0.8 liters in FF and 2.5 ± 0.3 liters in RH, P < 0.01] and convective O2 delivery (AUC, 0.30 ± 0.16 liters in FF and 0.54 ± 0.05 liters in RH, P < 0.01), were significantly increased in RH compared with FF. RH was also associated with significantly higher capillary blood flow (P < 0.05) and faster tissue reoxygenation mean response times (70 ± 15 s in FF and 24 ± 15 s in RH, P < 0.05). This resulted in a 43% increase in estimated peak mitochondrial ATP synthesis rate (29 ± 13 mM/min in FF and 41 ± 14 mM/min in RH, P < 0.05) whereas the phosphocreatine (PCr) recovery time constant in RH was not significantly different (P = 0.22). This comprehensive assessment of local skeletal muscle O2 availability and utilization in untrained subjects reveals that mitochondrial function, assessed in vivo by 31P-MRS, is limited by convective O2 delivery rather than an intrinsic mitochondrial limitation.
authors.affiliation: Department of Medicine, Division of Geriatrics, University of Utah, Salt Lake City, Utah;
authors.forename: Gwenael
authors.initials: G
authors.lastname: Layec
authors.forename: Luke J
authors.initials: LJ
authors.lastname: Haseler
authors.forename: Joel D
authors.initials: JD
authors.lastname: Trinity
authors.forename: Corey R
authors.initials: CR
authors.lastname: Hart
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Yann
authors.initials: Y
authors.lastname: Le Fur
authors.forename: Eun-Kee
authors.initials: EK
authors.lastname: Jeong
authors.forename: Russell S
authors.initials: RS
authors.lastname: Richardson
mesh_terms: D000328:Adult; D001783:Blood Flow Velocity; D004734:Energy Metabolism; D015444:Exercise / Q000502:physiology; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D006940:Hyperemia / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D007866:Leg; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism; D010101:Oxygen Consumption; D010725:Phosphocreatine / Q000378:metabolism; D019265:Spectroscopy, Near-Infrared; D014463:Ultrasonography; D055815:Young Adult
chemical_list: D006454:Hemoglobins; D010725:Phosphocreatine; C100003:deoxyhemoglobin
keywords: 31P-MRS; O2 delivery; PCr recovery kinetics; mitochondrial function; muscle energetics